We plan to continue studies of the immunopathogenesis of thyroid disease. We will place particular emphasis on the synthesis of antibodies in these conditions. We have developed a model of antithyroglobulin production by pokeweed mitogen-stimulated peripheral blood leukocytes in vitro. We plan to exploit this to learn more about the regulation of autoantibody production. We plan to assay other thyroid autoantibodies such as the antimicrosomal antibody and the anti-TSH receptor antibody with methods similar to those that we have developed for antithyroglobulin. All of these studies are designed to test the hypothesis that autoantibody production is due to some failure of immune regulation. The alternative hypothesis that alteration of the antigen may be responsible for the immunization will be studied by testing the immune clearance of thyroglobulin from patients with Hashimoto's thyroiditis in tolerant rabbits.